The physiological trauma that besets the human body as a result of surgery, cancer, intensive burns, radiation therapy and the like has a deleterious effect on the health of the individual in more ways than one. It is well known that patients recovering from such trauma and who are being therapeutically treated often have compromised host defense mechanisms. A damaged or reduced immune system can often lead to increased morbidity and eventual death as a result of infection and/or organ failure through rejection.
In a related case U.S. Pat. No. 5,231,085 also to Alexander et. al., the present applicants discovered novel immunomodulatory compositions and methods which enhance host defense mechanisms which have been compromised and are deficient for one reason or another. The immunomodulatory compositions are composed of an amino acid such arginine or ornithine that are used in the biosynthetic pathways of other polyamines, a nucleobase source and a combination of omega-3- and omega-6-polyunsaturated fatty acids. The composition is administered enterally or modified for parenteral administration and is preferably used as a supplement to a complete nutritional diet meeting the complete daily caloric and vitamin requirements of the patient. The administration of these compositions restore damaged or compromised immune systems to their healthy state. The Alexander et. al. '085 patent is hereby incorporated by reference.
The immunomodulatory compositions of Alexander et. al. '085 are believed to decrease the damage caused by the inflammatory response through multiple immune functional pathways. These compositions, when administered to surgery patients during the early post-operative period have been shown to bring about a significant reduction in the length of the average hospital stay as well as a significant reduction in the number of wound complications.
It is also well documented that the administration of lipids such as those found in a number of common fish oils significantly reduce the degree of immune response to solid organ allografts leading to improved survival. In one study, fish oil supplementation reduced the number of rejection episodes of renal allografts during the first year post-operative by 60%. Omega-3-polyunsaturated fatty acids which are found in these fish oils in fact have several properties which suggest that they play a key role in the inflammatory response. They are known to be potent inhibitors of platelet aggregation, thrombus formation and appear to reduce small vessel arteriosclerosis. These effects are presumed to occur through the down regulation of TxA-2 production in multiple cell lines.
Arginine and RNA precursors have also been associated with the enhancement of immune responses. Numerous studies have documented the significant role of arginine in immune system immunomodulation. Supplementing the diet with arginine has been noted to increase thymic weight as well as enhance T-cell responsive to mitogens. In in vitro models, arginine appears to be an absolute requirement for lymphocyte blastogenic response. Cancer patients undergoing major operative surgery who received enteral feedings supplemented with arginine experienced significant enhancement in T-cell activation to Con A and PHA stimulation. RNA precursors are also felt to be a rate-limiting metabolite in the propagation of immune cells and their supplementation has been associated with enhanced immune proliferation. Moreover, certain rapidly growing cells, such as T-lymphocytes appear to lack the ability to synthesize nucleotides and depend on salvage pathways to obtain sufficient amounts of nucleotides to continue growth.